Pyridine → methyl 5-bromo-6-chloro-1H-indole-3-carboxylate

To a stirred mixture of 5-bromo-6-chloro-1H-indole (60 g, 260 mmol), N,N-dimethylaminopyridine (3.21 g, 26.0 mmol), pyridine (56.5 mL, 703 mmol), and tetrahydrofuran (400 mL) was added in drops at 0° C. neat trichloroacetyl chloride (70.1 mL, 625 mmol). The obtained mixture was warmed to room temperature in 2 h (a precipitate began to form) and was stirred at room temperature for 3 days. Added in drops 110 ml of methanol at 0-10° C. followed by 70 ml of 25% sodium methoxide in methanol (680 mmol) at 0° C. The mixture was then stirred at 45° C. for 3 h. Then 250 ml of water and 200 ml of MTBE were added. The organic extract was separated, washed with brine, dried over magnesium sulfate, and concentrated at 50° C. and 90 mm Hg to ˜¼ of the initial volume. Precipitate was filtered off, washed with MTBE, and dried in vacuum at 45° C. to obtain the title compound (39.9 g, 53% yield). The mother liquor was concentrated to a heavy slurry. Methanol (400 ml) was added and the mixture was stirred at 65° C. for 4 h and slowly cooled to room temperature and stirred overnight. The solid was filtered off, washed with methanol, and dried in vacuo at 45° C. to obtain additional title compound (16.88 g, 22%). Total yield=75%. MS (ES−): 288.0, 290.0 (M+H)+1H NMR (500 MHz, DMSO-d6) ppm 12.17 (br. s, 1H), 8.26 (s, 1H), 8.18 (s, 1H), 7.74 (s, 1H), 3.82 (s, 3H).

1. customto form) and
2. stirringThe mixture was then stirred at 45° C. for 3 h
3. extractionThe organic extract
4. customwas separated
5. washwashed with brine
6. dry with materialdried over magnesium sulfate
7. concentrationconcentrated at 50° C.
8. filtrationPrecipitate was filtered off
9. washwashed with MTBE
10. customdried in vacuum at 45° C.

ORD record

ord-c6a19469aa9c44d59652dcc7d4745d82

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889730B2